Testing of luminescence imaging apparatus with automatic detection of a testing device

ABSTRACT

A solution is proposed for testing a luminescence imaging apparatus ( 105 ). A corresponding method ( 700 ) comprises acquiring ( 706 ) a photograph image and finding ( 708 ) a position of the testing device ( 110 ) in the photograph image. The 5method further comprises acquiring ( 706 ) a luminescence image and determining ( 734 - 736 ) a representation of sites of the testing device ( 110 ), each comprising at least one luminescence substance, in the luminescence image according to the position of the testing device ( 110 ) in the photograph image. The luminescence imaging apparatus ( 105 ) is then tested ( 754 - 772 ) according to the representation of the sites ( 330 ) in the 0luminescence image. A corresponding computer program ( 600 ) and a computer program product for implementing the method ( 700 ) are also proposed. Moreover, a testing device ( 110 ) for use in the method ( 700 ) is proposed.

TECHNICAL FIELD

The present disclosure relates to imaging applications. Morespecifically, this disclosure relates to luminescence imaging.

BACKGROUND ART

The background of the present disclosure is hereinafter introduced withthe discussion of techniques relating to its context. However, even whenthis discussion refers to documents, acts, artifacts and the like, itdoes not suggest or represent that the discussed techniques are part ofthe prior art or are common general knowledge in the field relevant tothe present disclosure.

Imaging generally relates to a number of techniques that allow acquiringimages of objects (typically, not visible directly) in a substantiallynon-invasive manner. For example, imaging techniques are routinelyexploited in equipment for medical applications to inspect (inner)body-parts of patients for diagnostic, therapeutic and/or surgicalpurposes.

A specific imaging technique increasingly considered is luminescenceimaging, and especially fluorescence imaging. Luminescence imaging isbased on a luminescence phenomenon, consisting of the emission of lightby luminescence substances when subject to any excitation different fromheating; particularly, a fluorescence phenomenon occurs in fluorescencesubstances (called fluorophores), which emit light when they areilluminated (with an intensity depending on an amount of thefluorophores that are illuminated). For example, this phenomenon isleveraged in medical applications by administering fluorescence agentsto the patients, and especially targeted fluorescence agents adapted toreaching a specific molecule of a desired target and then to remainingimmobilized thereon (for example, thanks to a specific interaction withtumoral tissues).

For this purpose, (fluorescence) imaging apparatuses are used; theimaging apparatuses allow illuminating each object to be imaged (with anexcitation light suitable to excite the fluorophores) and to acquirecorresponding (fluorescence) images representing the fluorophorespresent in the object, often together with (photograph) images simplyrepresenting the object; particularly, in medical applications thefluorescence images represent the fluorescent agent immobilized on thecorresponding target and the photograph images represent the body-partsunder analysis.

The imaging apparatuses should be tested to verify their performance.This is especially important in medical applications, wherein theperformance of the imagining apparatuses affects correspondingdiagnostic, therapeutic and/or surgical results.

The test of the imaging apparatuses may be carried out with specificmetering instruments. However, this does not allow verifying anillumination unit and an acquisition unit of the imaging apparatusessimultaneously. Another possibility is of using a curable polyurethanematrix or a composite phantom embedding quantum dots (small particlesmanufactured in a semiconductor process) in different concentrations,for example, as described in U.S. Pat. No. 9,167,240. However, thequantum dots exhibit a very high absorption of visible light(particularly, far higher than the one of the fluorescence agentstypically used in medical applications), so that they may be used toverify the performance of the imaging apparatuses only in environmentswith controlled illumination.

In order to test the imaging apparatuses in a close simulation of theiractual usage, it is instead possible to use samples of the samefluorophores to be imaged, i.e., the fluorescence agents in medicalapplications. Several testing devices are available for this purpose.For example, it is possible to use well plates (commonly used inlaboratories for other purposes), loosely arranged tubes or capillarytubes being filled with different concentrations of the fluorescenceagent. However, these testing devices require manual interventions (forexample, on-site preparations and selections of regions of interest inthe images), which are inconvenient and error-prone.

Moreover, “Setting Standard for Reporting and Quantification inFluorescence-Guided Surgery” by Hoogstings et al., Mol Imaging Biol(2019) 21:11-18 proposes the use of a testing device by SurgVisioncalled CalibrationDisk (trademarks thereof). This testing device isformed by an upper disk (holding eight tubes filled with differentconcentration of a fluorescence agent) and a base on which the upperdisk may rotate.

US-A-2003/146663 discloses a light calibration device, which comprisesan array of low-power light supplies each having a known emission.US-A-2008080781 discloses a fluorescence standard, which has at leasttwo areas with different fluorescent response. US-A-2007/200058discloses a phantom device, which includes a body and a fluorescentlight source internal to the body.

SUMMARY

A simplified summary of the present disclosure is herein presented inorder to provide a basic understanding thereof; however, the solepurpose of this summary is to introduce some concepts of the disclosurein a simplified form as a prelude to its following more detaileddescription, and it is not to be interpreted as an identification of itskey elements nor as a delineation of its scope.

In general terms, the present disclosure is based on the idea ofdetecting the testing device automatically.

Particularly, an aspect provides a method for testing a luminescenceimaging apparatus. The method comprises acquiring a photograph image andfinding a position of the testing device in the photograph image. Themethod further comprises acquiring a luminescence image and determininga representation of sites of the testing device, each comprising atleast one luminescence substance, in the luminescence image according tothe position of the testing device in the photograph image. Theluminescence imaging apparatus is then tested according to therepresentation of the sites in the luminescence image.

A further aspect provides a software program for implementing themethod.

A further aspect provides a corresponding software program product.

A further aspect provides a testing device for use in the method.

A further aspect provides a luminescence imaging system comprising theluminescence imaging apparatus and the testing device. Morespecifically, one or more aspects of the present disclosure are set outin the independent claims and advantageous features thereof are set outin the dependent claims, with the wording of all the claims that isherein incorporated verbatim by reference (with any advantageous featureprovided with reference to any specific aspect that applies mutatismutandis to every other aspect).

BRIEF DESCRIPTION OF THE DRAWINGS

The solution of the present disclosure, as well as further features andthe advantages thereof, will be best understood with reference to thefollowing detailed description thereof, given purely by way of anon-restrictive indication, to be read in conjunction with theaccompanying drawings (wherein, for the sake of simplicity,corresponding elements are denoted with equal or similar references andtheir explanation is not repeated, and the name of each entity isgenerally used to denote both its type and its attributes, such asvalue, content and representation). Particularly:

FIG. 1 shows a pictorial representation of a fluorescence imaging systemaccording to an embodiment of the present disclosure,

FIG. 2 shows a schematic block diagram of a fluorescence imagingapparatus that may be used to practice the solution according to anembodiment of the present disclosure,

FIG. 3 -FIG. 4 show different views of a testing device according to anembodiment of the present disclosure,

FIG. 5 shows a detail of the fluorescence imaging apparatus according toan embodiment of the present disclosure,

FIG. 6 shows the main software components that may be used to implementthe solution according to an embodiment of the present disclosure, and

FIG. 7A-FIG. 7C show an activity diagram describing the flow ofactivities relating to an implementation of the solution according to anembodiment of the present disclosure.

DETAILED DESCRIPTION

With reference in particular to FIG. 1 , a pictorial representation isshown of a (fluorescence) imaging system 100 according to an embodimentof the present disclosure. The imaging system 100 comprises a(fluorescence) imaging apparatus 105 known per se and a testing device110 according to an embodiment of the present disclosure.

The imaging apparatus 105 is used in medical applications to inspectbody-parts of patients (not shown in the figure), for example, fordiagnostic, therapeutic and/or surgical purposes. The imaging apparatus105 comprises the following components. A trolley 115 houses a supplyunit and a control unit (not visible in the figure) for supplying andcontrolling, respectively, the imaging apparatus 105. Four casters 120(only three visible in the figure) are arranged at corresponding lowercorners of the trolley 115 to facilitate moving the imaging apparatus105 (with a foot brake, not visible in the figure, that is provided forsecuring the imaging apparatus 105 in position). A pillar 125 extendsupwards from a back surface of the trolley 115. The pillar 125 has ahandlebar 130 for moving the imaging apparatus 105 by an operatorthereof. A cantilever 135 projects from the pillar 125, above thetrolley 115. A primary monitor 140 (for displaying images to theoperator) and a keyboard with a pointing device such as a mouse or atrackball 145 (for entering information/commands by the operator) aremounted on the cantilever 135. A pivoting arm 150 is mounted on top ofthe pillar 125 (above the cantilever 135). A secondary monitor 155 (fordisplaying images to a doctor, such as a surgeon) is mounted on thepivoting arm 150 (so as to allow turning it in either directions). Anarticulated arm 160 is mounted on top of the pillar 125 as well (next tothe pivoting arm 150). An imaging head 165 (for imaging a scene withinits field of view, and particularly the body-parts under analysis) issuspended from the articulated arm 160. The imaging head 165 is providedwith two handlebars 170 for positioning it by the operator.

The testing device 110 is used to test the imaging apparatus 105 forverifying its performance. For example, the test is aimed at calibratingthe imaging apparatus 105, at ensuring that the imaging apparatus 105operates correctly, at monitoring operation of the imaging apparatus 105over time and/or at comparing the imaging apparatus 105 with differentones. For this purpose, the testing device 110 is rested on a supportingsurface 175, so as to be positioned within the field of view of theimaging head 165; particularly, in the exemplary implementation shown inthe figure the supporting surface 175 is defined by a top surface of thetrolley 115.

With reference now to FIG. 2 , a schematic block diagram is shown of theimaging apparatus 105 that may be used to practice the solutionaccording to an embodiment of the present disclosure.

Particularly, the figure shows a functional structure of the imaginghead 165 and of the control unit, denoted with the reference 205.

Starting from the imaging head 165, it has an illumination unit and anacquisition unit for illuminating the scene in its field of view and foracquiring images thereof, respectively.

The illumination unit comprises the following components. An excitationlight source 210 and a white light source 215 generate an excitationlight and a white light, respectively. The excitation light haswavelength and energy suitable to excite the fluorophores of thefluorescence agent (such as of Near Infra-Red, or NIR, type), whereasthe white light appears substantially colorless to the human eye (suchas containing all the wavelengths of the spectrum that is visible to thehuman eye at equal intensity). Corresponding delivery optics 220 anddelivery optics 225 deliver the excitation light and the white light,respectively, to the (same) field of view of the imaging head 165.

The acquisition unit comprises the following components. Collectionoptics 230 collect light from the field of view (in an epi-illuminationgeometry). The collected light comprises fluorescence light that isemitted by any fluorophores present in the field of view. Indeed, thefluorophores pass to an excited (electronic) state when they absorb theexcitation light; the excited state is unstable, so that thefluorophores very shortly decay therefrom to a ground (electronic)state, thereby emitting the fluorescence light (at a characteristicwavelength, longer than the one of the excitation light because ofenergy dissipated as heat in the excited state) with an intensitydepending on an amount of the fluorophores that are illuminated.Moreover, the collected light comprises visible light (in the visiblespectrum) that is reflected by any object present in the field of view(illuminated by the white light). A beam-splitter 235 splits thecollected light into two channels. For example, the beam-splitter 235 isa dichroic mirror transmitting and reflecting the collected light atwavelengths above and below, respectively, a threshold wavelengthbetween a spectrum of the fluorescence light and a spectrum of thevisible light. In one of the channels of the beam-splitter 235 with the(portion of the) collected light in the spectrum of the fluorescencelight (such as the transmitted one), an emission filter 240 receives thefluorescence light and filters it to remove any excitation light (whichmight be reflected by objects in the field of view) and any ambientlights (which might be generated by background/inherent fluorescence). Afluorescence camera 245 receives the fluorescence light from theemission filter 240 and generates a corresponding fluorescence (digital)image representing the distribution of the fluorophores in the field ofview. In the other one of the channels of the beam-splitter 235 with the(portion of the) collected light in the spectrum of the visible light(such as the reflected one), a photograph camera 250 receives thevisible light and generates a corresponding photograph (digital) imagerepresenting a visualization of the objects in the field of view.

Moving to the control unit 205, it comprises several units that areconnected among them through a bus structure 255. Particularly, one ormore microprocessors (μP) 260 provide processing and orchestrationfunctionalities of the control unit 205. A non-volatile memory (ROM) 265stores basic code for a bootstrap of the control unit 205 and a volatilememory (RAM) 270 is used as a working memory by the microprocessors 260.The control unit 205 is provided with a mass-memory 275 for storingprograms and data (for example, a Solid-State-Disk, or SSD). Moreover,the control unit 205 comprises a number of controllers 280 forperipherals, or Input/Output (I/O) units; particularly, the controllers280 control the excitation light source 210, the white light source 215,the fluorescence camera 245 and the photograph camera 250 of the imaginghead 165; moreover, the controllers 280 control further peripherals,denoted as a whole with the reference 285, such as the primary monitor,the keyboard, the pointing device, the secondary monitor, a drive forreading/writing removable storage units (such as of USB type) and anetwork interface card (NIC) for connecting to a communication network(such as a LAN and then the Internet).

In operation, the imaging head 165 is used to image a body-part 290 of apatient 295 during an imaging process thereof (for example, a diagnosticanalysis, a therapeutic treatment or a surgical intervention). For thispurpose, a fluorescence agent is administered to the patient 295 (forexample, intravenously or locally). The fluorescence agent is atarget-specific fluorescence agent that is adapted to attaching to aspecific (biological) target by means of a specific interactiontherewith (such as tumoral tissues, nerves, blood-vessels, lymph-nodes,lymph-vessels and so on). The fluorescence agent is administered to thepatient 295 in advance (such as 24-72 hours before the imaging process),so as to allow the fluorescence agent to circulate within a vascularsystem of the patient 295 until reaching the body-part 290 and bindingto the desired target. During the imaging process, the imaging head 165is positioned to have the body-part 290 within its field of view. Atthis point, the body-part 290 is illuminated with both the excitationlight and the white light; fluorescence images (representing thedistribution of the fluorescence agent, and then of its target, in thebody-part 290) and photograph images (representing the visualization ofthe body-part 290) are acquired in succession. Thefluorescence/photograph images are then displayed onto theprimary/secondary monitors of the imaging apparatus, generally overlaidto each other into corresponding combined images (representing thetarget being contextualized on an anatomical structure of the body-part290).

With reference now to FIG. 3 -FIG. 4 , different views are shown of thetesting device 110 according to an embodiment of the present disclosure.

Starting from FIG. 3 , it shows a perspective view of the testing device110. The testing device 110 has a main body (for example, of plasticmaterial) defining a holder 305. The holder 305 has a (bottom) restingsurface 310 for resting the testing device 110 on any supportingsurface, for example, the supporting surface 175 of the trolley of theimaging apparatus, not shown in the figure; the holder 305 has a (top)imaging surface 315 opposite the resting surface 310 for imaging thetesting device 110. The testing device 110 has one or more sites eachcomprising at least one luminescence substance. Particularly, in theexemplary implementation shown in the figure one or more seats 320 (fourin this specific implementation, only one visible in the figure) areprovided in the holder 305. The seats 320 are configured to accommodatecorresponding containers 325 (one shown outside the seat 320 and threeshown inside the seats 320 in the figure). Each container 325 is filledwith a liquid containing a fluorescence agent (or more); for example,the containers 325 are of different types each defined by thecorresponding fluorescence agent and/or its concentration. The testingdevice 110 may be either in a basic version or in a complete version. Inthe basic version, the testing device 110 is provided without thecontainers 325 (to be acquired separately and then inserted into theseats 320 in a removable way). In the complete version, instead, thetesting device 110 is provided with the containers 325 already insertedin the seats 320 (either in a removable way or in a non-removable way).Windows 330 corresponding to the seats 320 are opened in the imagingsurface 315. Each window 330 exposes part of the corresponding seat 320;therefore, each window 330 also exposes a corresponding part of thecontainer 325 accommodated in the seat 320 so as to allow imaging itsfluorescence agent. For this purpose, at least the part of the container325 exposed through the window 330 is transparent to both the excitationlight and the fluorescence light (i.e., it is capable of allowing theexcitation/fluorescence light to pass through it substantially withoutbeing excessively diffused, such as with a ratio, between the radiantpower of a beam of excitation/fluorescence light exiting the container325 in a direction defined by a corresponding angle of refraction andthe radiant power of a beam of excitation/fluorescence light enteringthe same container 325 being slanted with respect to its surface, higherthan 80%, preferably higher than 85% and even more preferably higherthan 90%, such as between 95% and 100%).

In the solution according to an embodiment of the present disclosure,the holder 305 has one or more markers 335, 340 arranged on the imagingsurface 315 (for example, formed by corresponding labels stitchedthereon), which are machine-readable optically (for example, QR codes).The markers 335, 340 operate as positional markers for determining aposition (i.e., location and orientation) of the testing device 110.Particularly, in this specific implementation a (central) marker 335 isarranged at a central point of the holder 305 and four (window) markers340 are arranged in correspondence to the windows 330 (for example,alternated to each other). As described in detail in the following, themarkers 335, 340 may be used to detect the testing device 100 in acorresponding photograph image; this information then allows determininga representation of the windows 330 in a corresponding luminescenceimage for use to test the imaging apparatus 105 accordingly.

In the specific implementation of the testing device 110 shown in thefigure, one or more of the markers 335, 340 may further operate asinformative markers encoding (device) information of the testing device110. For example, one marker 335, 340 or multiple makers 335, 340 incombination encode a (unique) device identifier of the testing device110 (for example, with the device identifier encoded in the marker 335).The device identifier allows tracking a usage of the testing device 110.The testing device 110 may have either a free configuration or a fixedconfiguration. In the free configuration, any types of containers 325(with fluorescence agent of any nature and concentration) may bearranged in the seats 320. In a fixed configuration, instead,pre-defined types of containers 325 (with fluorescence agent of specificnature and concentration) are to be arranged in the seats 320. In thelatter case, one or more of the markers 335, 340 (either individually orin combination) encode (unique) container identifiers of the types ofcontainers 325 to be accommodated in the seats 320 (for example, witheach container identifier encoded in a corresponding marker 340 close toits seat 320). The container identifiers allow verifying the correctconfiguration of the testing device 110.

The markers 335, 340 are arranged at corresponding bottom surfaces ofrecesses (denoted with the same references), which extend from theimaging surface 315 inwards the holder 305 (downwards). The bottomsurfaces of the recesses 335, 340 are parallel to the resting surface310. Therefore, when the testing device 110 rests on the supportingsurface 175 (substantially horizontally), the bottom surfaces of therecesses 335, 340 are horizontal as well. This increases a visibility ofthe markers 335, 340 (when observed from above). Moreover, the recesses335, 340 have corresponding edges at the imaging surface 315 which arechamfered. For example, the edges are chamfered to form an angle of40-50° (such as of 45°) with the imaging surface 315. This reduces anyshadowing of the markers 335, 340 when the testing device 110 isilluminated from above.

The holder 305 has a shape (in plant view) having point symmetry; inthis specific implementation, the shape is octagonal, with four longedges and four short edges alternated to each other. The holder 305 thenhas a lateral surface 345 (extending between the resting surface 310 andthe imaging surface 315) with four big faces and four small facesalternated to each other (corresponding to the long edges and the shortedges, respectively). The seats 320 comprise corresponding blind holes,which extend inwards from the lateral surface 345, and more specificallyfrom the small faces thereof. The windows 330 comprise correspondingthrough-holes, which reach the seats 320 from the imaging surface 315.As a result, by placing a center of illumination of the imaging headdefining its optical axis (not show in the figure) at the central pointof the holder 305, it is possible to have a same illumination of all thecontainers 325 through the windows 330 (symmetric thereto).

The windows 330 are opened in portions of the imaging surface 315 thatare inclined with respect to the resting surface 310. For example, theportions of the imaging surface 315 around the windows 330 are orientedinwards the holder 305 (downwards) moving towards its central point, soas to form an angle with the resting surface 310 of 5-15° (such as 10°).This reduces a reflection of the imaging surface 315 (at least close tothe windows 330) when the testing device 110 is illuminated from above.

The windows 330 have corresponding edges at the imaging surface 315which are chamfered. For example, the edges are chamfered to form anangle of 40-50° (such as of 45°) with the imaging surface 315. Thisreduces any shadowing of the windows 330 when the testing device 110 isilluminated from above.

The testing device 110 comprises a testing light source 350 at theimaging surface 315, which testing light source 350 generates a testinglight of the same type as the fluorescence light emitted by one or morefluorescence agents when illuminated by the excitation light (i.e., ofNIR type). For example, the testing light source 350 is based on a frameof LEDs running around the marker 335; the testing light source 350 issupplied by a replaceable/non-replaceable battery enclosed in the holder305 and is turned on/off by acting on a switch (not visible in thefigure). The testing light source 350 may be used to test theacquisition unit of the imaging apparatus alone (with its illuminationunit turned off).

In the fixed configuration of the testing device 110, the holder 305 hascorresponding seat indicators 355 on the imaging surface 315 (forexample, formed by corresponding labels stitched thereon), which arehuman-readable (for example, in text form). The seat indicators 355 arearranged in correspondence to the seats 320 and provide a specificationof the types of containers 325 to be accommodated therein. Particularly,the seat indicators 355 are color-coded; for example, the seatindicators 355 contain color names corresponding to the types ofcontainers 325 (such as white, yellow, blue and green for increasingconcentrations of a same fluorescence agent). The seat indicators 355facilitate the insertion of the correct types of containers 325 into theseats 320 (especially when the testing device 110 is assembled on thefield).

In any (free/fixed) configuration of the testing device 110, thecontainers 325 have corresponding container indicators, which arehuman-readable (for example, colors). The container indicators arearranged on parts of the containers 325 projecting from the seats 320when the containers 325 are inserted therein (so as to remain visible)and provide a specification of their types. Particularly, the containerindicators are again color-coded. For example, corresponding caps 360 ofthe containers 325 are colored according to the types of containers 320as above, i.e., white, yellow, blue and green for increasingconcentrations of the fluorescence agent (in this case, discernible bypeople affected by protanopia as well). The container indicators furtherfacilitate the insertion of the correct types of containers 325 in thecorresponding seats 320; moreover, they also allow verifying that thetesting device 110 has been assembled correctly at any time.

Moving to FIG. 4 , it shows a cross-section view of the same testingdevice 110; particularly, the cross-section view is in a (vertical)symmetry plane, perpendicular to the resting surface 310, of two opposedseats 320 (one with the container 325 outside it and the other one withthe container 325 inside it in the figure). The seats 320 are inclinedwith respect to the resting surface 310 (i.e., a longitudinal axisthereof is not parallel to the resting surface 310). Because of theinclination of the seats 320, the containers 325 accommodated thereinare inclined with respect to the resting surface 315 as well. Therefore,when the testing device 110 rests on the supporting surface 175(substantially horizontally), the containers 325 are not horizontal.Moreover, each window 330 is spaced apart from a distal (top) end of thecorresponding seat 320, more distant from the resting surface 310 thananother proximal (bottom) end thereof. As a result, any impurities thatmay be present in the containers 325 (such as air bubbles and smallfloating particles) naturally flow upwards and accumulate there, awayfrom the corresponding windows 330. This ensures that the parts of thecontainers 325 that are imaged through the windows 330 are substantiallyfree of impurities. Moreover, the containers 325 may not be filledcompletely; in this case as well, air remaining in the containers 325flows upwards and accumulate there, away from the corresponding windows330. This ensures that the parts of the containers 325 that are imagedthrough the windows 330 are substantially full of the fluorescenceagent. All of the above significantly increases a quality of the imagingof the containers 325, which reflects in an improved accuracy of anytests of the imaging apparatus performed with the testing device 110.

Particularly, the longitudinal axes of the seats 320 form an inclineangle α of 5-30°, preferably 7-20° and still more preferably 9-15°, suchas 10°, with the supporting surface 175. These values of the inclineangle α provide a fast flowing upwards of the impurities and the air(for example, so as to allow using containers 325 even filled by 70-90%only); at the same time, they do not adversely affect the imaging of thecontainers 325.

A distance of the windows 330 (i.e., their upper borders) from thedistal end of the corresponding seats 320 is 10-50%, preferably 20-40%and still more preferably 25-35%, such as 30% of a length of the seats320 (along their longitudinal axis). These values of the distance ensurethat any impurities and/or air in the containers 325 are never imaginedthrough the windows 330 in most practical situations.

Each seat 320 has an external portion 405 with a constant section (forexample, with a cylindrical shape) and an internal portion 410 with asection decreasing moving inwards the holder 305 (for example, with afrusto-conical shape). The corresponding window 330 exposes at leastpart of the external portion 405 of the seat 320. The containers 325accommodated in the seats 320 have a matching shape. For example, thecontainers 325 are commercial off-the-shelf vials of 1.5 ml. Each vial325 comprises a (transparent) elongated bottle 415 (such as of plasticmaterial) containing the liquid with the fluorescence agent, which vial325 is closed by the cap 360 (for example, of screw-on type).Accordingly, the bottle 415 has a top portion 420 (proximal to anopening thereof) with a constant section (for example, with acylindrical shape) and a bottom portion 425 (distal from the opening)with a section decreasing moving away from the opening (for example,with a frusto-conical shape). Therefore, the windows 330 expose at leastpart of the top portions 420 of the containers 325 (and particularlytheir lowest part). In this way, the containers 325 are imaged wherethey are substantially flat.

One or more magnetic elements 430 (two in this specific implementation)are embedded in the holder 305, close to the resting surface 310. Whenthe supporting surface 175 is of ferromagnetic material (such as iron),the magnetic elements 430 generate an attraction force that maintainsthe testing device 110 (rested thereon) fixed in position.

With reference now to FIG. 5 , a detail is shown of the imagingapparatus 105 according to an embodiment of the present disclosure.

The imaging apparatus 105 has a holding station 505, which is used tohold the testing device 110 in a fixed (imaging) position on thesupporting surface 175; the testing device 110 is held in the imagingposition in a removable way. For example, the holding station 505 isformed by a recess matching a footprint of the testing device 110(defined by its resting surface, not visible in the figure), possiblywith the addition of four lateral hollows for avoiding any interferenceof the parts of the containers 325 projecting from the holder 305; inthis way, the testing device 110 may be inserted into the holdingstation 505 by dropping it into the recess. The recess has a depth lowerthan a height of the holder 305; in this way, the testing device 110 maybe removed from the holding station 505 by grasping and lifting it fromthe recess.

Moreover, the imaging apparatus 105 has a (further) holding station 510,which is used to hold the imaging head 165 in an (acquisition) position;the imaging head 165 as well is held in the acquisition position in aremovable way. For example, the holding station 510 is formed by a ringmatching a main body of the imaging head 165 (excluding its handlebars170); the ring is integral with a cantilever 515 fixed to the pillar 125of the testing device 110. In this way, the imaging head 165 may beinserted into the holding station 510 by sliding it into the ring fromabove, until the handlebars 170 abut against it; moreover, the imaginghead 165 may be removed from the holding station 510 by lifting it untilleaving the ring.

Alternatively (not shown in the figure), the holding station 505 and theholding station 510 may be combined into a single structure for holdingboth the testing device 110 in the imaging position and the imaging head165 in the acquisition position. For example, this result may beachieved by a cylinder which is closed at the bottom by a base having arecess for inserting the testing device 110 and it is open at the topfor sliding the imaging head 165 as above.

When the testing device 110 is in the imaging position (defined by theholding station 505) and the imaging head 165 is in the acquisitionposition (defined by the holding station 510), the testing device 110falls within the field of view of the imaging head 165. Particularly,the central point of the holder 305 is on the optical axis of theimaging head 165. This provides a controlled and repeatable illuminationof the testing device 110.

With reference now to FIG. 6 , the main software components are shownthat may be used to implement the solution according to an embodiment ofthe present disclosure.

All the software components (programs and data) are denoted as a wholewith the reference 600. The software components 600 are typically storedin the mass memory and loaded (at least in part) into the working memoryof the control unit of the imaging apparatus when the programs arerunning, together with other software components not directly relevantto the solution according to the present disclosure (such as anoperating system, medical applications and so on), which other softwarecomponents are omitted for the sake of simplicity. The programs areinitially installed into the mass memory, for example, from removablestorage units or from the communication network (not shown in thefigure). In this respect, each program may be a module, segment orportion of code, which comprises one or more executable instructions forimplementing the specified logical function.

Particularly, corresponding drives, denoted as whole with the reference605, are used to drive the peripherals of the imaging apparatus,comprising its excitation light source, white light source, fluorescencecamera, photograph camera, keyboard, pointing device, primary/secondarymonitors and network interface card. An imaging manager 610 managesimaging processes of any body-parts. The imaging manager 610 interfaceswith the drives 605. The imaging manager 610 accesses (in read/writemode) an imaging repository 615, which stores a sequence of fluorescenceimages and photograph images being acquired during an imaging processthat is in progress.

In the solution according to an embodiment of the present disclosure, atesting manager 620 manages any tests of the imaging apparatus. Thetesting manager 620 as well interfaces with the drives 605. The testingmanager 620 accesses (in read/write mode) an image repository 625, aconfiguration repository 630 and a log repository 635. The imagerepository 625 stores one or more fluorescence images and photographimages that are acquired during a test of the imaging apparatus that isin progress. The configuration repository 630 stores configurationinformation for the tests of the imagining apparatus. For example, theconfiguration information comprises a network address (such as a domainname) of a remote service provider (for example, a server of amanufacturer of the imaging apparatus), a descriptor of the testingdevice and a descriptor of the containers. The descriptor of the testingdevice indicates it by the corresponding device identifier. Thedescriptor of the testing device defines its configuration, i.e., freeor fixed. The descriptor of the testing device defines its geometry; forexample, the geometry of the testing device is defined in terms of shapeof its holder and in terms of position of the windows, the markers, theseat indicators and the caps with respect to the holder (for example,their real-word coordinates in a reference system integral therewith).The descriptor of the testing device defines a specification of thecontainers for the markers, the seat indicators and the containerindicators; for example, for each possible type of container there areprovided its container identifier for the markers, its color name forthe corresponding seat indicator and its color definition for thecorresponding container indicator (the latter in terms of nominal valuesof one or more statistical parameters relating thereto, such mean valueof color components, like RGB components). The descriptor of the testingdevice defines one or more usage rules thereof (for example, maximumusage in terms of length of the tests, maximum elapsed time from aproduction date and so on). The descriptor of the testing device definesone or more characteristics of each testing light generated by itstesting light source (for example, wavelength and nominal values of oneor more statistical parameters relating thereto, such as meanfluorescence intensity, or MFI). The descriptor of the containersdefines each possible type of them; for example, each type of container(identified by its container identifier) is defined by nature and/orconcentration of the corresponding fluorescence agent and by afluorescence specification of the fluorescence light emitted by it (interms of wavelength and nominal values of one or more statisticalparameters relating thereto, such as mean fluorescence intensity). Thelog repository 635 stores information about the tests that have beenperformed by the imaging apparatus 105. For example, the log repository635 has a record for each test (for example, identified by itstimestamp); the record comprises a length of the test, an indication ofa result of the test and a change flag (which is asserted when the testhas been performed with a new testing device and/or with newcontainers). The testing manager 620 exploits an object recognitionengine 640, which is used to find the position of the testing device inphotograph/fluorescence images thereof. The object recognition engine640 accesses (in read mode) the configuration repository 630 and itaccesses (in write mode) a transformation repository 645, which is alsoaccessed (in read mode) by the testing manager 620. The transformationrepository 645 stores a definition of a transformation between thereal-word coordinates of the testing device and corresponding imagecoordinates in the fluorescence/photograph images (for example, in theform of a transformation matrix).

With reference now to FIG. 7A-FIG. 7C, an activity diagram is showndescribing the flow of activities relating to an implementation of thesolution according to an embodiment of the present disclosure.

Particularly, the activity diagram represents an exemplary process thatmay be used to test the imaging apparatus with a method 700. In thisrespect, each block may correspond to one or more executableinstructions for implementing the specified logical function on thecontrol unit of the imaging apparatus.

The process is executed whenever the imaging apparatus has to be tested.For example, this may happen before any imaging process, after aninstallation or any maintenance of the imaging apparatus, upon request,periodically and so on, either in response to a corresponding request orautomatically (as described in the following). In this event, theoperator places the testing device onto the supporting surface and theimaging head above it (for example, by inserting the testing device andthe imaging head into the corresponding holding stations if available).The operator then enters a test command with the keyboard or thepointing device; the test command may also specify a type of the test,selected between a test in a single position or a test throughout thefield of view of the imaging head (for example, the first one bydefault). At the same time, the operator may also select a correspondingcommand when the containers or the whole testing device have beenchanged, in the latter case together with its device identifier. In anycase, the test command is received at block 702 by the testing managervia the corresponding drive.

In response thereto, the process passes to block 704 wherein the testingmanager initializes a temporary record for the test, with its time-stamp(set to a current time from an internal clock), start time (set to thesame current time) and change flag (asserted if the containers or thetesting device have been changed or deasserted otherwise); moreover, ifthe testing device has been changed, the testing manager downloads anindication of the (free/fixed) configuration of the testing device fromthe service provider (from its network address retrieved from theconfiguration repository) according to the device identifier, and thenupdates the descriptor of the testing device in the configurationrepository accordingly. The testing manager at block 706 turns on thewhite light source and the excitation light source, and it commands thephotograph camera and the fluorescence camera to acquire a photographimage and a fluorescence image, respectively, of their same field ofview (via the corresponding drives), after that the testing managerturns off the white light source and the excitation light source. Thephotograph image is defined by a bitmap comprising a matrix of cells(for example, with 512 rows and 512 columns) each storing a value of apixel, i.e., a basic picture element corresponding to a location of thefield of view, which pixel value represents the visible light reflectedby the location (such as its RGB components). The fluorescence image isdefined by a bitmap comprising a matrix of cells (with either the sameor different size with respect to the photograph image) each storing apixel value representing the fluorescence light emitted by thecorresponding location of the field of view (such as its intensity). Theobject recognition engine at block 708 searches for the testing devicein the photograph image, i.e., its representation in a correspondingRegion Of Interest (ROI), by exploiting image processing techniquesknown per se based on the known geometry of the testing device (asdefined by its descriptor in the configuration repository). The testingmanager at block 710 verifies whether the testing device has been found.Particularly, the image recognition engine may simply search for theholder of the testing device (according to its shape). In addition or inalternative, the image recognition engine searches for the markers(according to their specification) and verifies whether they are correct(i.e., in the right number and with the right format). The markers makethe detection of the testing device more accurate (with respect to theuse of the holder), especially when they are multiple (like the fivemarkers in the example at issue). If the testing device has not beenfound (i.e., no holder and/or no correct markers), the process returnsto the block 706 to repeat the same operations continually, up to apre-defined time-out, after that the process returns to the block 702(not shown in the figure) with the testing manager that displays anerror message on the primary monitor (via the corresponding drive).

The same operations may also be performed to start the testautomatically in response to an appearance of the testing device withinthe field of view of the imaging head. For this purpose, in anon-operative condition of the imaging apparatus (i.e., when no imagingprocess is in progress), the testing manager monitors the field of viewby continually performing a corresponding loop. The loop begins at block712, wherein the testing manager turns on the white light source and theexcitation light source, and it commands the photograph camera and thefluorescence camera to acquire a photograph image and a fluorescenceimage, respectively, of their same field of view (via the correspondingdrives), after that the testing manager turns off the white light sourceand the excitation light source. The object recognition engine at block714 searches for the testing device in the photograph image as above.The testing manager at block 716 verifies whether the testing device hasbeen found. If the testing device has not been found, the processreturns to the block 712 to repeat the same operations periodically (forexample, every 5-10 s). Conversely, as soon as the testing device hasbeen found, the process descends into block 718. At this point, thetesting manager initializes the temporary record with its time-stamp andstart time as above, and with the type of test set to the singleposition and the change flag deasserted. This allows starting the testby simply presenting the testing device into the field of view of theimaging head, without the need of any additional intervention by theoperator.

In any case, the process continues to block 720 from the block 710 (assoon the testing device has been found) or from the block 718. At thispoint, the testing manager determines a current position of the testingdevice with respect to the imaging head according to its representationin the photograph image (with image-processing techniques known per se);for example, the current position is defined by a location of thecentral point of the testing device in an imaging plane perpendicular tothe optical axis of the imaging head, a distance of the testing devicefrom the imaging head and a rotation angle of the testing device withrespect to the imaging plane. This operation is completely automatic,and then fast and accurate. The testing manager at block 722 verifieswhether the current position matches a target position (such as definedby the central point of the testing device on the optical axis of theimaging head, the testing device at a certain distance from the imaginghead and parallel to its imaging plane). For example, the testingmanager calculates a corresponding displacement between the currentposition and the target position as defined by translation and rotationcomponents, and compares them with corresponding pre-defined thresholds(such as 0.1-1 cm and 1-5°). If one or more translation/rotationcomponents exceed the corresponding thresholds (meaning that the currentposition does not match the target position), the testing manager atblock 724 displays a corresponding message on the primary monitor (viathe corresponding drive). The message indicates a movement of thetesting device and/or of the imaging head (given by the displacement),which is required for reaching the target position; for example, whenthe central point of the testing device is not on the optical axis ofthe imaging head, the operator is required to translate it, whereas whenthe testing device is not at the correct distance/angle with respect tothe imaging head, the operator is required to translate/rotate thelatter. The process then returns to the block 706 to repeat the sameoperations. In this way, the operator is provided with a very usefulfeedback, which allows placing the testing device and/or the imaginghead in a correct reciprocal position even when no holding stations areavailable.

Referring back to the block 722, if all the translation/rotationcomponents do not exceed the corresponding thresholds (meaning that thecurrent position matches the target position), the process descends intoblock 726; particularly, this is always true when the testing device andthe imaging head are inserted into the corresponding holding stations.At this point, the testing manager extracts the device identifier fromthe markers in the photograph image. The testing manager at block 728retrieves usage information of the testing device from the logrepository (for example, length of the tests that have been performedsince a last change of the testing device or of its containers). Inaddition or in alternative, the testing manager downloads (further)usage information of the testing device from the service provider (fromits network address retrieved from the configuration repository)according to its device identifier (assuming that it matches the onestored in the configuration repository); for example, this usageinformation may comprise an authenticity indicator of the testing deviceand its production date. The testing manager at block 730 verifies theusage information (retrieved and/or downloaded) against the usage rules(retrieved from the configuration repository); for example, the testingmanager compares the length of the tests (since the last change of thetesting device or of its containers) and/or a time elapsed from theproduction date with the corresponding maximum allowable values. Thetesting monitor then enables the test according to a result of thisverification. If any usage rule is not satisfied (always true when thedevice identifier does not match the one stored in the configurationrepository), the testing manager at block 732 aborts the test anddisplays a corresponding error message on the primary monitor (via thecorresponding drive); the process then returns to the block 702 waitingfor a next test command. Alternatively, as shown in dashed line in thefigure, the testing manager simply displays a corresponding warningmessage on the primary monitor (via the corresponding drive), but thetest is still allowed by continuing to block 734. The same point is alsoreached directly from the block 730 if all the usage rules aresatisfied.

At this point, the testing manager generates the transformation matrix(between the real-word coordinates of the testing device and the imagecoordinates in its fluorescence/photograph images); for example, thetransformation matrix is calculated by minimizing a mapping errorbetween the real-word coordinates of the markers in the testing device(retrieved from the configuration repository) and the image coordinatesof the markers in the photograph image (such as the mean square value oftheir differences). This operation may be based on a single marker withasymmetric readout (providing location and orientation of the testingdevice according to its specification); however, the use of multiplemarkers (like the five markers in the example at issue) adds furtheraccuracy. The testing manager at block 736 further determines the seatindicators and the caps in the photograph image and the windows in thefluorescence image (i.e., their representations in corresponding ROIs)according to their image coordinates therein calculated by applying thetransformation matrix to the corresponding real-word coordinates(retrieved from the configuration repository).

The automatic detection of the position of the testing device in thephotograph image and the automatic determination of the representationof the windows in the luminescence image accordingly avoid any humanintervention for selecting the desired regions of interest. Thisexpedites the test and makes it less prone to errors, with a beneficialeffect on its cost and quality.

The testing manager now verifies the containers arranged in the seats.For this purpose, the testing manager at block 738 calculates the samestatistical parameters, of the color definitions for the containerindicators in the configuration repository, for the pixel valuesrepresenting each cap in the photograph image, i.e., mean values oftheir RGB components in the example at issue. The flow of activitybranches at block 740 according to the configuration of the testingdevice (retrieved from the configuration repository). If the testingdevice has the free configuration, the testing manager at block 742estimates the types of containers arranged in the seats. For example,the testing manager calculates a distance between the colors of the capsin the photograph image and the color definitions of every permutationof four types of containers among all the possible ones defined in theconfiguration repository (such as equal to the mean square value of thedifferences between the mean values of the RGB components of each capand the corresponding nominal values of the color definition of thecorresponding type of container); the testing manager selects thepermutation that provides the lowest distance. Referring back to theblock 740, if the testing device has the fixed configuration, thetesting manager at block 744 extracts the container identifiers from themarkers in the photograph image (indicating the types of containers thatshould be arranged in the seats). In this phase, the testing manager mayalso read the color names from the seat indicators in the photographimage (indicating the same expected types of containers that should bearranged in the seats). The testing manager verifies whether each pairof corresponding color name and container identifier refers to the sametype of container (as indicated in the configuration repository). Ifnot, the process returns to the block 702 (not shown in the figure) withthe testing manager that displays an error message on the primarymonitor (via the corresponding drive). In this way, it is possible toensure that the testing device (in the fixed configuration) has beenassembled correctly. The flow of activity then merges at block 746 fromeither the block 742 or the block 744; at this point, a loop is enteredwith the testing manager that takes a (current) seat into account(starting from a first one in any arbitrary order). The testing managerat block 748 verifies whether the container arranged in the seat is ofthe expected type (i.e., the estimated one in the free configuration orthe read one in the fixed configuration). For this purpose, the testingmanager verifies whether the color of the cap matches the colordefinition of the expected type of container (retrieved from theconfiguration repository); for example, the testing manager calculates adifference between the mean value of each RGB component of the cap andthe corresponding nominal value of the color definition, and comparesthem with a pre-defined threshold (such as 1-5% with respect to thecolor definition). If one or more differences exceed the threshold(meaning that the container is not of the expected type), the testingmanager at block 750 aborts the test and displays a corresponding errormessage on the primary monitor (via the corresponding drive); theprocess then returns to the block 702 waiting for a next test command.Conversely, if no difference exceeds the threshold (meaning that thecontainer is of the expected type), the testing manager at block 752verifies whether a last seat has been processed. If not, the processreturns to the block 746 to repeat the same operations for a next seat.Conversely, once all the seats have been processed (determining that allthe containers of the expected types are arranged therein), the loop isexit by descending into block 754.

At this point, the testing manager verifies the windows in thefluorescence image. For this purpose, the testing manager calculates thesame statistical parameters, of the fluorescence specification for thecorresponding type of container in the configuration repository, for thepixel values representing each window in the fluorescence image, i.e.,mean fluorescence intensity in the example at issue; moreover, thetesting manager calculates the same statistical parameters (i.e., meanfluorescence intensity) for the pixel values representing a backgroundarea different from the windows in the photograph image (for example,coincident with the central marker). A loop is then entered at block 756with the testing manager that takes a (current) window into account(starting from a first one in any arbitrary order). The testing managerat block 758 verifies whether the window matches the fluorescencespecification of the type of container arranged in the seat (retrievedfrom the configuration repository); for example, the testing managercalculates a difference between the mean fluorescence intensity of thewindow and the corresponding nominal value of the type of container, andcompares it with a pre-defined threshold (such as 1-5% with respect tothe fluorescence specification). In addition or in alternative, thetesting manager calculates the ratios between the mean fluorescenceintensity of the (current) window and the mean fluorescence intensity ofeach other window and of the background area; the testing managerfurther calculates the ratios between the corresponding nominal values(retrieved from the configuration repository for the types of containersof the other windows and set to almost zero for the background area).The testing manager then calculates a difference between each pair ofratios, and compares it with a pre-defined threshold (such as 1-5% withrespect to the ratio of the nominal values). In any case, the testingmanager adds a result of these verifications to the temporary record forthe test. The testing manager at block 760 verifies whether a lastwindow has been processed. If not, the process returns to the block 756to repeat the same operations for a next window. Conversely, once allthe windows have been processed, the loop is exit by descending intoblock 762.

At this point, the testing manager verifies an alignment between thephotograph image and the fluorescence image. For this purpose, theobject recognition engine searches for the markers (i.e., theirrepresentations in corresponding ROIs) in the fluorescence image (asabove). The testing manager at block 764 verifies whether the markers inthe photograph image match the corresponding markers in the fluorescenceimage; for example, the testing manager calculates a distance betweeneach marker in the photograph image and in the fluorescence image asdefined by a mean value of corresponding translation components, andcompares it with a pre-defined threshold (such as 1-5% of a maximumextent of the marker in the photograph image). The testing manager addsa result of this verification to the temporary record of the test.

The testing manager at block 766 may perform additional verifications ofthe imaging apparatus (according to the photograph image). For example,the testing manager determines a contrast of the acquisition unitaccording to a difference between the brightest pixel values and theleast bright pixel values of the marks in the photograph image. In casethe marks are tilted with respect to the row/columns of the photographimage (by an angle known from the geometry of the testing deviceretrieved from the configuration repository), the testing devicedetermines the depth of field of the acquisition unit by applying theslanted edge method. The testing device may have a spatial resolutiontarget on its imaging surface (for example, the 1951 USAF, IEEE or ISOone), which is further specified in the configuration repository; inthis case, the object recognition engine searches for the spatialresolution target (i.e., its representation in a corresponding ROI) inthe photograph image, and the testing manager then determines thespatial resolution of the acquisition unit according thereto. Thetesting device may have a color test target on its imaging surface(either distinct or combined with the spatial resolution target), whichis further specified in the configuration repository; in this case, theobject recognition engine searches for the color test target (i.e., itsrepresentation in a corresponding ROI) in the photograph image, and thetesting manager then determines the color resolution of the acquisitionunit according thereto. The testing device may have a reflectancestandard on its imaging surface (either distinct or combined with thespatial resolution target and/or the color target), which is furtherspecified in the configuration repository. In this case, the objectrecognition engine searches for the reflectance standard (i.e., itsrepresentation in a corresponding ROI) in the photograph image. Thetesting manager determines an ambient light as a difference between thewhite light generated by the white light source (as further defined inthe configuration repository in terms of one or more statisticalparameters relating thereto, such as its mean intensity) and acorresponding reflected light received from the reflectance standard (asdefined by the same statistical parameters for the pixel valuesrepresenting it in the photograph image, i.e., mean intensity in theexample at issue). The testing manager then compares the ambient light(defined by the values of the statistical parameters for the reflectedlight minus the values of the corresponding statistical parameters forthe white light) with a pre-defined threshold (such as 1-5% of thevalues of the statistical parameters for the white light). In additionor in alternative, the same operation may also be performed bydetermining the ambient light as a difference between the excitationlight generated by the excitation light source (as further defined inthe configuration repository in terms of one or more statisticalparameters relating thereto, such as its mean intensity) and acorresponding (further) reflected light received from the reflectancestandard (as defined by the same statistical parameters for the pixelvalues representing it in the fluorescence image, i.e., mean intensityin the example at issue). This allows verifying that the ambientconditions are suitable for correct operation of the imaging apparatus.In any case, the testing manager adds a result of these verifications tothe temporary record of the test.

The testing manager at block 768 displays a message on the primarymonitor (via the corresponding drive), requiring the operator to turn onthe testing light source (via the corresponding switch of the testingdevice). As soon as the testing light source has been turned on, theprocess continues to block 770. For example, this may happen in responseto a corresponding command entered by the operator with the keyboard orthe pointing device (received by the testing manager via thecorresponding drive). Alternatively, this may happen automatically bymonitoring the field of view with a corresponding loop which isperformed continually (for example, every 1-2 s). Particularly, for thispurpose the testing manager commands the fluorescence camera to acquirea fluorescence image of its field of view with the excitation lightsource turned off (via the corresponding drives), and then calculatesthe mean intensity of the fluorescence image; these operations arerepeated until the mean intensity exceeds a threshold, such as 2-3 timesthe one corresponding to typical ambient fluorescence. In both cases,the testing manager now commands the fluorescence camera to acquire a(further) fluorescence image of its field of view (via the correspondingdrives), while the white light source and the excitation light sourceare turned off. The testing manager verifies the acquisition unit aloneof the imaging apparatus according to this luminescence image and thecharacteristics of the testing light (retrieved from the configurationrepository); for example, the testing manager calculates a differencebetween the mean fluorescence intensity of the fluorescence image andits nominal value, and then compares this difference with apre-determined threshold (such as 5-10% with respect to the nominalvalue). The testing manager adds a result of this verification to thetemporary record of the test. The testing manager at block 772 verifiesthe illumination unit alone of the imaging apparatus according to theabove-mentioned verifications of the imaging apparatus (as a whole) andof its acquisition unit (alone). For example, the testing managerconditions the statistical parameters (mean fluorescence intensity)calculated above for the pixel values representing each window in theprevious fluorescence image (step 754) according to the differencebetween the same mean fluorescence intensity of the (current)fluorescence image and its nominal value (so as to remove the effect ofany mismatch of the acquisition unit); the testing manager then verifiesagain whether each window matches the fluorescence light emitted by thecontainer arranged in the corresponding seat as above (steps 756-760).The testing manager adds a result of this verification to the temporaryrecord of the test.

The flow of activity branches at block 774 according to the type of test(as indicated in the temporary record). If the test has to be performedthroughout the field of view of the imaging head, the testing manager atblock 776 verifies whether it has been completed (i.e., the imagingapparatus has already been tested in all a set of predefined positionsthroughout the field of view, such as in a matrix with a pitch of 1-5 cmalong every direction). If not, the testing manager at block 778determines a movement of the testing device (according to the pitch) forreaching a further (new) position throughout the field of view; thetesting manager then displays a corresponding message on the primarymonitor (via the corresponding drive). As soon as the testing device hasbeen moved to the new position, the process returns to the block 706 torepeat the same test of the imaging apparatus in its new position. Forexample, this may happen in response to a corresponding command enteredby the operator with the keyboard or the pointing device (received bythe testing manager via the corresponding drive). Alternatively, thismay happen automatically by monitoring the field of view with acorresponding loop which is performed continually (for example, every1-2 s). Particularly, for this purpose the testing manager turns on thewhite light, commands the photograph camera to acquire a photographimage of its field of view and then turns off the white light source(via the corresponding drives), the object recognition engine searchesfor the testing device in the photograph image, the testing managerverifies whether the testing device has been found and if so whether thecurrent position of the testing device matches the new position (asabove); these operations are repeated until the testing device has beenfound in the new position. The process instead descends into block 780from the block 776 once the test has been completed (in all thepositions throughout the field of view) or directly from the block 774if the test has to be performed in a single position. In any case, thetesting manager now determines a length of the test, from its start time(from the temporary record) to the current time (from the internalclock); the testing manager adds the length of the test to the temporaryrecord.

The testing manager at block 782 saves the result of the test defined inthe temporary record by adding it to the log repository. The testingmanager at block 784 transmits the result of the test to the serviceprovider (to its network address retrieved from the configurationrepository). This allows implementing telemetric applications fortracking operation of the imaging apparatus remotely. The testingmanager at block 786 displays the result of the test on the primarymonitor (via the corresponding drive). The operator may then reactaccordingly. For example, if the result of the test indicates that theperformance of the imaging apparatus is good, the corresponding imagingprocess may be performed (with a high degree of confidence on theinformation provided by the imaging apparatus). Conversely, the imagingprocess is aborted (since the information provided by the imagingapparatus might be misleading) and the operator may request anintervention to a support center of the manufacturer of the imagingapparatus. The process then returns to the block 702 waiting for a nexttest command.

All of the above allows verifying the performance of the imagingapparatus with a high accuracy and in a reproducible manner. In thisway, it is possible to detect any degradation of the performance of theimaging apparatus (for example, caused by corrupted light sources, dirtydelivery/collection optics, mechanical wearing, parasitic light and soon), even when the degradation is not noticeable by the operator.

Modifications

Naturally, in order to satisfy local and specific requirements, a personskilled in the art may apply many logical and/or physical modificationsand alterations to the present disclosure. More specifically, althoughthis disclosure has been described with a certain degree ofparticularity with reference to one or more embodiments thereof, itshould be understood that various omissions, substitutions and changesin the form and details as well as other embodiments are possible.Particularly, different embodiments of the present disclosure may evenbe practiced without the specific details (such as the numerical values)set forth in the preceding description to provide a more thoroughunderstanding thereof; conversely, well-known features may have beenomitted or simplified in order not to obscure the description withunnecessary particulars. Moreover, it is expressly intended thatspecific elements and/or method steps described in connection with anyembodiment of the present disclosure may be incorporated in any otherembodiment as a matter of general design choice. Moreover, itemspresented in a same group and different embodiments, examples oralternatives are not to be construed as de facto equivalent to eachother (but they are separate and autonomous entities). In any case, eachnumerical value should be read as modified according to applicabletolerances; particularly, unless otherwise indicated, the terms“substantially”, “about”, “approximately” and the like should beunderstood as within 5-10%. Moreover, each range of numerical valuesshould be intended as expressly specifying any possible number along thecontinuum within the range (comprising its end points). Ordinal or otherqualifiers are merely used as labels to distinguish elements with thesame name but do not by themselves connote any priority, precedence ororder. The terms include, comprise, have, contain, involve and the likeshould be intended with an open, non-exhaustive meaning (i.e., notlimited to the recited items), the terms based on, dependent on,according to, function of and the like should be intended as anon-exclusive relationship (i.e., with possible further variablesinvolved), the term a/an should be intended as one or more items (unlessexpressly indicated otherwise), and the term means for (or anymeans-plus-function formulation) should be intended as any structureadapted or configured for carrying out the relevant function.

For example, an embodiment provides a method for testing a luminescenceimaging apparatus. However, the luminescence imaging apparatus may be ofany type (see below) and it may be tested for any purpose and at anytime (for example, for calibration after installation/maintenance, forverification before every use, for monitoring/comparison over time andso on); moreover, the method may be invoked in any way (for example, inresponse to any start command entered via any input unit of thefluorescence imaging apparatus, such as its keyboard, any pointingdevice, a dedicated button and the like, automatically, in any case withor without the possibility of entering information, such as the type oftest or the change of the testing device, and so on).

In an embodiment, the method is performed with a testing device placedwithin a field of view of an imaging head of the luminescence imagingapparatus. However, the testing device may be of any type (for example,with or without any positional markers); moreover, the imaging head maybe of any type (see below) and the testing device may be placed withinits field of view in any way (for example, by exploiting correspondingholding stations, freely, by moving either the testing device and/or theimaging head and so on).

In an embodiment, the testing device has an imaging surface for imagingthe testing device. However, the imaging surface may be of any type (seebelow).

In an embodiment, the imaging surface is provided with one or more siteseach comprising at least one luminescence substance. However, the sitesmay be in any number and of any type (see below).

In an embodiment, the method comprises the following steps under thecontrol of a control unit of the luminescence imaging apparatus.However, the control unit may be of any type (see below).

In an embodiment, the method comprises acquiring (with a photographcamera of the imaging head) a photograph image of the field of viewrepresentative of a reflected light being reflected by the field ofview. However, the photograph image may be of any type (for example,with any size, in colors or black-and-white, in 2D or 3D, with anypixel/voxel values, such as RGB components, luminance components, and soon) and it may be acquired with any photograph camera (see below).

In an embodiment, the method comprises retrieving a descriptor of thetesting device. However, the descriptor may be retrieved in any way (forexample, by reading locally, downloading remotely, and so on).

In an embodiment, the descriptor comprises an indication of a geometryof the testing device. However, the geometry of the testing device maybe defined in any way only by the shape of the testing device (forexample, when the shape allows determining both location and orientationof the testing device, such as having no point symmetry like with aprojection/recess at a first one of the sites defining a sequencethereof), only by the positional markers (for example, in any number, ofany type and arranged at any position allowing determining both locationand orientation of the testing device as below), by characteristicpoints of the testing device (for example, its corners), by anycombination thereof (for example, the shape of the testing device fordetermining the location and the positional markers for determining theorientation) and so on.

In an embodiment, the descriptor comprises an indication of a positionof the sites in the testing device. However, the position of the sitesin the testing device may be indicated in any way (for example, withrespect to the positional markers, the holder and so on).

In an embodiment, the method comprises finding a position of the testingdevice in the photograph image according to the geometry of the testingdevice. However, the position of the testing device may be found in anyway (for example, by applying any object recognition technique such asmodel-based, appearance-based, feature-based and the like, geneticalgorithms and so on).

In an embodiment, the method comprises calculating a position of thesites in the photograph image according to the position of the testingdevice in the photograph image and the position of the sites in thetesting device. However, the position of the sites in the photographimage may be calculated in any way (for example, by determining and thenapplying any transformation between real-word coordinates and imagecoordinates, such as of affine or non-rigid type, defined by a matrix, atransform, a vector and so on).

In an embodiment, the method comprises acquiring (with a luminescencecamera of the imaging head) a luminescence image of the field of view.However, the luminescence image may be of any type (either the same ordifferent with respect to the luminescence image, such as in terms ofsize, colors/black-and-white, 2D/3D, pixel/voxel values, in a singlecolor or in corresponding different colors for multiple fluorescenceagents, and so on) and it may be acquired with any luminescence camera(see below) either at the same time of or separately from the photographimage.

In an embodiment, the fluorescence image is representative of aluminescence light that is emitted by the luminescence substance of thesites in response to an excitation light thereof provided by anexcitation light source of the imaging head. However, the excitationlight may be of any type and it may be provided by any excitation lightsource (see below).

In an embodiment, the method comprises determining a representation ofthe sites in the luminescence image according to the position of thesites in the photograph image. However, the representation of the sitesin the luminescence image may be determined in any way according to theposition of the sites in the photograph image (for example, directly, bycorrecting possible misalignments between the two images, and so on).

In an embodiment, the method comprises testing the luminescence imagingapparatus according to the representation of the sites in theluminescence image. However, this operation may be performed in any way(for example, by comparing the representation of each site withcorresponding nominal values, with the representation of one or moreother sites, with the representation of a background area, anycombination thereof, in a single position or throughout the field ofview, and so on).

Further embodiments provide additional advantageous features, which mayhowever be omitted at all in a basic implementation.

In an embodiment, the method comprises retrieving the descriptorcomprising a specification of the positional markers. However, thepositional markers may be defined in any way (for example, by theirposition, orientation, format and so on).

In an embodiment, the method comprises retrieving the descriptorcomprising an indication of a position of the sites with respect to thepositional markers. However, the position of the sites with respect tothe positional markers may be indicated in any way (for example, bytheir displacement, the coordinates of the positional markers and thecoordinates of the sites in the testing device, and so on).

In an embodiment, the method comprises finding a position of thepositional markers in the photograph image according to thespecification of the positional markers. However, this operation may beperformed in any way (see above).

In an embodiment, the method comprises calculating the position of thesites in the photograph image according to the position of thepositional markers in the photograph image and the position of the siteswith respect to the positional markers. However, this operation may beperformed in any way (see above).

In an embodiment, the method comprises testing the luminescence imagingapparatus according to a comparison of the representation of each of thesites in the luminescence image with at least one nominal value.However, the nominal values may be in any number and of any type (forexample, any statistical parameters, such as mean, variance, standarddeviation, minimum/maximum values, median and so on); the test may beperformed accordingly in any way (for example, by comparing thedifference of each statistical parameter individually or a globaldifference with any threshold, and so on).

In an embodiment, the method comprises testing the luminescence imagingapparatus according to a comparison of the representation of each of thesites in the luminescence image with the representation of at leastanother one of the sites in the luminescence image. However, therepresentation of the sites may be compared in any way (for example,according to any statistical parameters of the sites as above, bycomparing any relationship (such as ratio, difference and the like) withany threshold and so on).

In an embodiment, the method comprises determining a representation of abackground area (different from the representations of the sites) in theluminescence image. However, the background area may be of any type (forexample, corresponding to any positional marker or independenttherefrom, and so on) and it may be determined in any way (for example,already given by the positional markers when coincident with one ofthem, according to the position of the testing device and to thedescriptor comprising an indication of a position of the background areain the testing device, by searching it directly and so on).

In an embodiment, the method comprises testing the luminescence imagingapparatus according to a comparison of the representation of each of thesites in the luminescence image with the representation of thebackground area in the luminescence image. However, this operation maybe performed in any way (either the same or different with respect tothe comparison with the other sites).

In an embodiment, the testing device comprises one or more containerscorresponding to the sites, each filled with a liquid comprising thecorresponding luminescence substance. However, the containers may be ofany type and filled with any luminescence substances (see below).

In an embodiment, the method comprises estimating corresponding expectedtypes of the containers according to a comparison of the representationsof the sites in the luminescence image with a plurality of pre-definedspecifications of possible types of the containers. However, theexpected types of the containers may be estimated in any way (forexample, by selecting them together (as the closest combination) orindividually (as the closest one) according to any criterion, and soon).

In an embodiment, the testing device has one or more opticallymachine-readable informative markers at the imaging surface. However,the informative markers may be in any number and of any type (seebelow).

In an embodiment, the method comprises determining a representation ofthe informative markers in the photograph image. However, theinformative markers may be determined in any way (for example, alreadygiven by the positional markers when coincident with them, according tothe position of the testing device and to the descriptor comprising anindication of a position of the informative markers in the testingdevice, by searching them directly and so on).

In an embodiment, the method comprises determining device informationrelating to the testing device according to the representation of theinformative markers. However, the device information may be of any type(see below) and it may be determined in any way (for example, extractedfrom the informative markers directly, retrieved according theretoeither locally or remotely, and so on).

In an embodiment, the method comprises testing the luminescence imagingapparatus according to the device information. However, the deviceinformation may be used in any way (for example, to determine expectedtype of containers, to retrieve usage rules, to retrieve usageinformation and so on).

In an embodiment, the method comprises determining expected types of thecontainers according to the device information. However, the type of thecontainers may be determined in any way (for example, directly from thedevice information, retrieved according thereto either locally orremotely, such as via corresponding container identifiers, and so on).

In an embodiment, the method comprises testing the luminescence imagingapparatus according to pre-defined specifications of the expected typesof the containers. However, the specifications of the types ofcontainers may be of any type (for example, nominal values of any numberand type of corresponding statistical parameters) and they may beretrieved in any way (for example, locally or remotely);

moreover, the test may be performed accordingly in any way (for example,by comparing the difference of each statistical parameter individuallyor any global difference with any threshold, and so on).

In an embodiment, the method comprises determining a representation ofcorresponding end portions of the containers projecting fromcorresponding seats of the testing device in the photograph image.However, the end portions may be of any type (see below) and they may bedetermined in any way (for example, according to the position of thetesting device and to the descriptor comprising an indication of aposition of the end portions in the testing device, by searching themdirectly and so on).

In an embodiment, the method comprises verifying a configuration of thetesting device according to a matching of the representation of the endportions in the photograph image with pre-defined definitions of thecorresponding expected types of the containers. However, the definitionsof the types of containers may be of any type (for example, colordefinitions given by any number and type of statistical parameters,color names and so on) and they may be retrieved in any way (forexample, locally or remotely); the verification of the configuration ofthe testing device may be performed accordingly in any way (for example,by comparing the difference of each statistical parameter individuallyor a global difference with any threshold, by comparing the names, withor without the further verification of the seat indicators, and so on).

In an embodiment, the method comprises finding a position of the testingdevice in the luminescence image. However, the position of the testingdevice may be found in the luminescence image in any way (either thesame or different with respect to the photograph image).

In an embodiment, the method comprises testing the luminescence imagingapparatus according to an alignment between the photograph image and theluminescence image determined according to the position of the testingdevice in the photograph image and the position of the testing device inthe luminescence image. However, this operation may be performed in anyway (for example, by comparing the distance between each pair ofcorresponding markers individually, any global value based on thedistances between all the pairs of corresponding markers, a distancebetween the holders and the like with any threshold, and so on).

In an embodiment, the method comprises retrieving one or more usagerules of the testing device. However, the usage rules may be in anynumber and of any type (for example, maximum usage in terms of length oftests or number of tests, down to a single one when the testing deviceis disposable, elapsed time from a production date, expiration date andso on), and they may be retrieved in any way (for example, by readinglocally, downloading remotely, indiscriminately or according to thedevice identifier, and so on).

In an embodiment, the method comprises enabling said testing theluminescence imaging apparatus according to the usage rules. However,the test may be enabled according to the usage rules in any way (forexample, by verifying the usage rules in any way, such as requiringcompliance with all or only part of them, by enabling the test in anyway according to the corresponding result, such as preventing it, simplywarning the operator, notifying the service provider, any combinationthereof, and so on).

In an embodiment, the method comprises retrieving usage information ofone or more previous executions of said testing the luminescence imagingapparatus. However, the usage information may be of any type (forexample, length of tests, number of tests, date of last test and so on)and it may be retrieved in any way (for example, locally or remotely,and so on).

In an embodiment, the method comprises enabling said testing theluminescence imaging apparatus according to the usage information.However, the test may be enabled according to the usage information inany way (for example, by verifying it against any usage rules as above,with the usage rules that may be pre-defined locally or remotely,retrieved according to the device identifier, and by enabling the testin any way according to the corresponding result as above, and so on).

In an embodiment, the method comprises saving the usage information ofsaid testing the luminescence imaging apparatus. However, the usageinformation may be saved in any way (for example, individually orincrementally, locally or remotely, and so on).

In an embodiment, the method comprises retrieving the usage rules and/orthe usage information according to the device information. However, theusage rules and the usage information may be retrieved in any way (forexample, extracted directly from the device information, determinedaccording thereto either locally or remotely, such as via acorresponding device identifier, and so on).

In an embodiment, the testing device comprises a testing light source atthe imaging surface for generating a testing light corresponding to theluminescence light. However, the testing light source may be of any type(see below).

In an embodiment, the method comprises acquiring a further luminescenceimage of the field of view (with the luminescence camera) while theexcitation light source is turned off and the testing light source isturned on. However, the further luminesce image may be acquired at anytime (either before or after the luminesce image).

In an embodiment, the method comprises testing an acquisition unit ofthe imaging head (for acquiring the luminescence images) according tothe further luminescence image and predefined characteristics of thetesting light source. However, the acquisition unit may be of any type(see below); the characteristics of the testing light source may be ofany type (for example, nominal values of any number and type ofstatistical parameters) and they may be retrieved in any way (forexample, locally or remotely); moreover, the test may be performedaccordingly in any way (for example, by comparing the difference of eachstatistical parameter individually or a global difference with anythreshold, and so on).

In an embodiment, the method comprises testing an illumination unit ofthe imaging head (for generating the excitation light) according to aresult of said testing the luminescence imaging apparatus and a resultof said testing the acquisition unit. However, the illumination unit maybe of any type (see below) and it may be tested in any way (for example,by conditioning the representation of the sites according to the test ofthe acquisition unit and then repeating the test of the wholeluminescence imaging apparatus, by extrapolating it from the previoustest of the whole luminescence imaging apparatus according to the testof the acquisition unit, and so on).

In an embodiment, the method comprises determining a displacement of thetesting device and/or the imaging head from a target position accordingto the position of the testing device in the photograph image. However,the displacement may be determined in any way (for example, for eachcoordinate or globally, and so on) from the position of the testingdevice defined in any way (for example, by the holder and/or thepositional markers) to any target position thereof (for example,retrieved locally or remotely, inserted manually and so on); moreover,the displacement may be defined for the testing device alone, theimaging head alone or both of them.

In an embodiment, the method comprises outputting an indication of amovement of the testing device and/or the imaging head for reaching thetarget position according to the displacement thereof on an output unitof the luminescence imaging apparatus. However, the movement may be ofany type (for example, translation and/or rotation in plane or space forthe testing device alone, the imaging head alone or both of them, and soon); moreover, the indication of the movement may be output in any way(for example, displayed, uttered and so on) on any output unit (forexample, monitor, loudspeaker and so on). This feature may be used forany purpose (for example, to arrange the testing device correctly, totest the fluorescence imaging apparatus throughout the field of view andso on).

In an embodiment, the method comprises outputting an indication of aresult of said testing the luminescence imaging apparatus on an outputunit of the luminescence imaging apparatus. However, the result may beof any type (for example, simply passed/failed or with more or lessdetails about every verification); moreover, the result may be output inany way (for example, displayed, printed and so on) on any output unit(for example, monitor, printer and so on) and for any purpose (forexample, for enabling a corresponding imaging process, requesting amaintenance of the luminescence imaging apparatus either manually orautomatically, such as by message, e-mail and the like, and so on).

In an embodiment, the method comprises transmitting an indication of aresult of said testing the luminescence imaging apparatus to a remotecomputing system over a telecommunication network. However, the resultmay be of any type (either the same or different with respect to above)and it may be transmitted to any remote computing system in any way (forexample, by uploading it, via e-mail and so on) over any network (forexample, the Internet, a LAN and so on).

In an embodiment, the method comprises repeating the following loop in anon-operative condition of the luminescence imaging apparatus. However,the loop may be repeated with any frequency in any non-operativecondition (for example, when no imaging process is in progress asindicated by corresponding start and stop commands entered by theoperator via any input unit, in stand-by and so on).

In an embodiment, the loop comprises acquiring a further photographimage of the field of view with the photograph camera. However, thefurther photograph image may be of any type (either the same ordifferent with respect to the photograph image) and it may be acquiredin any way (for example, alone or with a corresponding fluorescenceimage to be used for the test after exiting the loop, and so on).

In an embodiment, the loop comprises searching a representation of thetesting device in the further photograph image according to the geometryof the testing device. However, the testing device may be searched inany way according to its descriptor (either the same or different withrespect to above for determining its position).

In an embodiment, the loop is performed until the representation of thetesting device in the further photograph image has been found. However,the exit condition of the loop be defined in any way (for example,according to a match of the shape of the testing device, a match of thepositional markers, both of them, and so on).

In an embodiment, the method comprises triggering said testing theluminescence imaging apparatus in response to the representation of thetesting device in the further photograph image being found. However, thetest may be trigged in any way (for example, automatically or requiringa manual confirmation, with or without prompting the operator to enterinformation, and so on).

Generally, similar considerations apply if the same solution isimplemented with an equivalent method (by using similar steps with thesame functions of more steps or portions thereof, removing somenon-essential steps or adding further optional steps); moreover, thesteps may be performed in a different order, concurrently or in aninterleaved way (at least in part).

An embodiment provides a computer program that is configured for causinga control unit of a luminescence imaging apparatus to perform theabove-mentioned method when the computer program is executed on thecontrol unit. An embodiment provides a computer program productcomprising a computer readable storage medium embodying a computerprogram, the computer program being loadable into a working memory of acontrol unit of a luminescence imaging apparatus thereby configuring thecontrol unit to perform the same method. However, the software programmay be implemented as a stand-alone module, as a plug-in for apre-existing software program (for example, the imaging manager), oreven directly in the latter. In any case, similar considerations applyif the software program is structured in a different way, or ifadditional modules or functions are provided; likewise, the memorystructures may be of other types, or may be replaced with equivalententities (not necessarily consisting of physical storage media). Theprogram may take any form suitable to be used by any control unit (seebelow), thereby configuring the control unit to perform the desiredoperations; particularly, the program may be in the form of external orresident software, firmware or microcode (either in object code or insource code, for example, to be compiled or interpreted). Moreover, itis possible to provide the program on any computer readable storagemedium. The storage medium is any tangible medium (different fromtransitory signals per se) that may retain and store instructions foruse by the control unit. For example, the storage medium may be of theelectronic, magnetic, optical, electromagnetic, infrared, orsemiconductor type; examples of such storage medium are fixed disks(where the program may be pre-loaded), removable disks, memory keys (forexample, of USB type), and the like. The program may be downloaded tothe control unit from the storage medium or via a network (for example,the Internet, a wide area network and/or a local area network comprisingtransmission cables, optical fibers, wireless connections, networkdevices); one or more network adapters in the control unit receive theprogram from the network and forward it for storage into one or morestorage devices of the control unit. In any case, the solution accordingto an embodiment of the present disclosure lends itself to beimplemented even with a hardware structure (for example, by electroniccircuits integrated in one or more chips of semiconductor material), orwith a combination of software and hardware suitably programmed orotherwise configured.

An embodiment provides a testing device for testing a luminescenceimaging apparatus. However, the testing device may be of any shape (forexample, with point symmetry or not), size and material (for example,plastic, resin, metal, paper and so on); moreover, the testing devicemay be used to test any luminescence imaging apparatus for any purpose(see above).

In an embodiment, the testing device has an imaging surface for imagingthe testing device. However, the imaging surface may be of any type (forexample, continuous or discontinuous, flat or non-flat, parallel orinclined with respect to the resting surface, and so on).

In an embodiment, the imaging surface is provided with one or more siteseach comprising at least one luminescence substance. However, the sitesmay be in any number and of any type. For example, the sites may becontainers arranged in corresponding seats and exposed through windowsthereof (see below); alternatively, the sites may be rigid/solidfluorescence samples or substrates (such as of paper, textile or anyother porous material wherein fluorescence substances are deposited,such as by printing, and possibly protected by a lamination/sealinglayer) arranged, removably or non-removably, in corresponding seats orpermanently embedded in the holder, and so on. Each site may contain anynumber and types of luminescence substances (for example, based on anyluminescence phenomenon, such as fluorescence, phosphorescence,chemiluminescence, bio-luminescence, induced Raman-radiation, with thesites containing the same luminescence substances in differentconcentrations and/or with different luminescence substances, and soon).

In an embodiment, the testing device comprises one or more opticallymachine-readable positional markers at the imaging surface (fordetermining a position of the testing device). However, the positionalmarkers may be in any number, of any type (for example, codes, signs andso on) and arranged at any position (for example, at the center, at thesites and/or at the peripheral of the testing device); the positionalmarkers may be used in any way for determining the position of thetesting device (for example, its location defined by one or morepositional markers, its orientation defined by multiple positionalmarkers and/or format of one or more positional markers, any combinationthereof and so on).

Further embodiments provide additional advantageous features, which mayhowever be omitted at all in a basic implementation.

In an embodiment, the testing device comprises a resting surfaceopposite the imaging surface for resting the testing device on asupporting surface. However, the resting surface may be of any type (forexample, continuous or discontinuous, flat, defined by projectingsupport elements, such as feet, balls and the like, with recesses, andso on) and it may be used to rest the testing device in any way (forexample, freely, in a holding station, locked thereto, and so on) on anysupporting surface (either part of the luminescence imaging apparatus orseparate therefrom, such as a table, a shelf and so on).

In an embodiment, the testing device comprises one or more seats.However, the seats may be of any shape (for example, with any section,such as circular, squared and so on, being constant, varying or both ofthem), of any size and at any position (for example, open laterally, onthe bottom, arranged regularly or not, and so on).

In an embodiment, the testing device comprises one or more containerseach filled with a liquid comprising the corresponding luminescencesubstance. However, the containers may be of any shape/size (either thesame as or simply compatible with the ones of the seats), of anymaterial (for example, of plastic, glass and so on) and of any type (forexample, vials, tubes, bottles and so on); moreover, the containers maybe filled at any level with any liquid containing any number ofluminescence substances.

In an embodiment, each of the containers is accommodated in acorresponding one of the seats. However, the containers may be in anynumber (either the same or lower than the number of the seats) and theymay be accommodated in the seats in any way (for example, in a removableway, non-removable way, a combination thereof, and so on).

In an embodiment, the testing device comprises one or more windowscorresponding to the seats (defining the corresponding sites). However,the windows may be of any type (for example, with or without chamferededges), size and shape (for example, circular, squared and so on).

In an embodiment, the windows are opened in the imaging surface.However, the windows may be opened at any position (for example, in acentral area of the seats, at an end thereof, along all the seats and soon).

In an embodiment, each of the windows exposes a part of thecorresponding seat for imaging the luminescence substance of acorresponding part of the container accommodated therein beingtransparent to an excitation light of the luminescence substance and toa luminescence light emitted by the luminescence substance whenilluminated by the excitation light. However, the exposed part of eachseat may have any extent (up to the whole seat). The containers may betransparent (at any extent) in any part thereof comprising the one to beimaged through the windows (up to completely), to any wavelengthscomprising the ones of the excitation/luminescence light (for example,to the visible light as well).

In an embodiment, the seats extend along corresponding longitudinal axesfrom corresponding first ends to corresponding second ends. However, theends of each seat may be arranged in any position (for example, at thecenter and the border of the testing device, spaced apart from them, anycombination thereof and so on).

In an embodiment, each of the seats is slanted with respect to theresting surface with the second end closer to the resting surface thanthe first end. However, the seats may be slanted in any way (forexample, downwards or upwards moving inwards the testing device) and atany angle.

In an embodiment, the corresponding windows are spaced apart from thefirst ends of the seats. However, the windows may be at any distancefrom the corresponding ends of the seats. In any case, the features ofthe inclined seats with the spaced-apart windows may also be implementedindependently, in a testing device without any positional marker.

In an embodiment the longitudinal axes of the seats form an angle of5-30° with the resting surface. However, the possibility is not excludedof having the seats forming a different angle with the resting surface.

In an embodiment, a distance of the corresponding windows from thesecond ends of the seats is 10-50% of a length of the seats. However,the possibility is not excluded of having the windows at differentdistance from these ends of the seats.

In an embodiment, the testing device has a lateral surface extendingbetween the resting surface and the imaging surface. However, thelateral surface may be of any type (for example, continuous ordiscontinuous, perpendicular to the resting surface, inclinedinwards/outwards the testing device and so on).

In an embodiment, the seats comprise corresponding blind holes extendinginwards from the lateral surface. However, the possibility is notexcluded of having the seats formed in another way (for example, bythrough-holes, recesses and so on).

In an embodiment, each of the seats comprises a first portion with aconstant section. However, the first portion may be of any length and atany position (for example, internal or external).

In an embodiment, each of the seats comprises a second portion with asection decreasing moving inwards the testing device. However, thesecond portion may be of any length and at any position (according tothe ones of the first portion); moreover, its section may decrease inany way (for example, regularly or non-regularly, at any rate up tobecome null, and so on).

In an embodiment, the corresponding window exposes at least part of thefirst portion. However, the window may expose any part of the firstportion (up to completely).

In an embodiment, the windows have corresponding edges at the imagingsurface that are chamfered. However, the chamfered edges may form anyangle with the imaging surface.

In an embodiment, the testing device has a point symmetry with respectto a central point. However, the testing device may have any shape withpoint symmetry (for example, octagonal, hexagonal, squared, circular andso on).

In an embodiment, the positional markers comprise a central positionalmarker corresponding to the central point. However, the centralpositional marker may be of any type (for example, at the center of thetesting device, around it and so on).

In an embodiment, the positional markers comprise one or more sitespositional markers corresponding to the sites. However, the sitepositional markers may be of any type (for example, with each sitebetween a pair of corresponding site positional markers, each sitepositional marker close to a corresponding site, and so on).

In an embodiment, the testing device comprises one or more opticallymachine-readable informative markers at the imaging surface encodingdevice information relating to the testing device. However, theinformative markers may be in any number and of any type (for example,incorporated in the positional markers and/or separated therefrom); theinformative markers may encode any device information (for example,device identifier of the testing device, container identifiers for theseats, usage rules of the testing device, proof of authenticity of thetesting device, type of containers for the seats and so on); the deviceinformation may be provided in any way (for example, QR codes, ArUcocodes, bar codes and so on).

In an embodiment, the device information comprises a device identifierof the testing device. However, the device identifier may be of any type(for example, a serial number, an encrypted code and so on); the deviceidentifier may be provided by any informative markers (for example, asingle informative marker, a combination of two or more of theinformative markers, and so on).

In an embodiment, the device information comprises correspondingcontainer identifiers of expected types of the containers to beaccommodated in the seats. However, the container identifiers mayindicate the types of containers in any way (for example, concentrationof (pre-defined) luminescence substances, nature and/or concentration of(varying) luminescence substances, product number of the containers andso on); the container identifiers may be provided by any informativemarkers (for example, a single informative marker, a combination of twoor more informative markers, a corresponding informative marker for eachseat, either the same as or different from the informative markersproviding the device identifier, and so on).

In an embodiment, the positional markers and/or the informative markersare arranged on corresponding bottom surfaces of recesses extending fromthe imaging surface. However, the recesses may be of any type (forexample, with or without chamfered edges), size and shape (for example,circular, squared and so on, either the same as or simply compatiblewith the ones of the markers) and depth; in any case, the possibility isnot excluded of having more markers arranged in each recess, or evenhaving the markers (or at least part of them) arranged flush with theimaging surface.

In an embodiment, the bottom surface is parallel to the resting surface.However, the possibility is not excluded of having the bottom surfaceinclined with respect to the resting surface.

In an embodiment, the recesses have corresponding edges at the imagingsurface that are chamfered. However, the chamfered edges may form anyangle with the imaging surface.

In an embodiment, the testing device comprises one or more lockingelements for locking the testing device on the supporting surface.However, the locking elements may be in any number, arranged at anyposition and of any type (for example, at the resting surface, at thelateral surface and the like, for locking the testing devicemagnetically, mechanically, such as with springs, clips, screws, Velcrostrips, suction cups, multi-use adhesives, and so on).

In an embodiment, the locking elements comprise corresponding magneticelements arranged at the resting surface. However, the magnetic elementsmay be in any number and at any positions, and they may be used togenerate any attraction force with the supporting surface (when made offerromagnetic material).

In an embodiment, the imaging surface around the windows is inclinedwith respect to the resting surface. However, the imaging surface aroundthe windows may form any angle with the resting surface (down to beparallel thereto).

In an embodiment, the testing device comprises one or morehuman-readable seat indicators corresponding to the seats. However, theseat indicators may be arranged in any position (for example, on theimaging surface, on the lateral surface and so on).

In an embodiment, the seat indicators provide correspondingspecifications of expected types of the containers to be accommodated inthe seats. However, the seat indicators may specify the types ofcontainers in any way (for example, with colors, names, codes and soon).

In an embodiment, the testing device comprises a testing light source atthe imaging surface for generating a testing light corresponding to theluminescence light. However, the testing light source may be of any typeand arranged at any position (for example, at the center or at theperiphery of the testing device); the testing light may be of any type(for example, fixed or variable, such as via a wireless commandtransmitted by the luminescence imaging apparatus selecting the testinglight in response to a manual command or according to predefinedcharacteristics of the excitation light source of the luminescenceimaging apparatus).

In an embodiment, the corresponding containers are accommodated in theseats in a non-removable way. However, the containers may beaccommodated in the seats in any non-removable way (for example, fixedmechanically, glued, integral and so on).

In an embodiment, the corresponding containers are accommodated in theseats in a removable way. However, the containers may be accommodated inthe seats in any removable way (for example, freely, snap fitted, with aselective blocking system and so on).

In an embodiment, the containers have corresponding end portionsprojecting from the seats. However, the end portions may be of any type(for example, caps, external ends of bottles/tubes and so on) and theymay project from the seats at any extent (down to none).

In an embodiment, the end portions are with human-readable containerindicators providing corresponding specifications of the containers.However, the container indicators may be of any type (either the same ordifferent with respect to the seat indicators).

In an embodiment, the seat indicators are color-coded. However, thecolors may be of any type and indicated in any way (for example, bytheir names, samples and so on).

In an embodiment, the container indicators are color-coded. However, thecolors may be of any type and indicated in any way (for example, withthe end portions themselves that are colored, with labels with theirnames, samples and so on).

In an embodiment, the containers comprise corresponding bottlescontaining the liquid and caps closing the bottles. However, the bottlesand the caps may be of any type (for example, with the bottles shapedlike vials or tubes, the caps that are screwed or press-fitted, and soon).

In an embodiment, the caps are colored according to the containerindicators. However, the caps may be colored in any way (for example,completely, laterally, on the top and so on).

An embodiment provides a luminescence imaging apparatus comprising acontrol unit configured for performing each step of the above-mentionedmethod. However, the luminescence imaging apparatus may be of any type(for example, a medical equipment, an industrial equipment and the like,for use in any luminescence applications, such as fluorescenceapplications in diagnostics, therapy or surgery, and so on); theluminescence imaging apparatus may comprise any control unit (forexample, any integrated central unit, any separate computer, such as anindustrial PC, and so on), any illumination unit (for example, based onlaser, LEDs, UV/halogen/Xenon lamp, and so on), any acquisition unit(for example, based on any number and type of lenses, wave guides,mirrors, CCD, ICCD, EMCCD, CMOS, InGaAs or PMT sensors, and so on), anyimaging head (for example, mounted on articulated arm, pivoting arm,stand-alone with wireless connection, hand-held and so on) and anyoutput device (for example, monitor, printer, network connection,head-mounted projector, and so on).

Further embodiments provide additional advantageous features, which mayhowever be omitted at all in a basic implementation.

Particularly, in an embodiment the luminescence imaging apparatuscomprises a supporting surface for resting the testing device. However,the supporting surface may be of any type (for example, a top surface ofany trolley, a cantilever, either fixed or hidden, and so on).

In an embodiment, the luminescence imaging apparatus comprises a holdingstation for holding the testing device in an imaging position on thesupporting surface in a removable way. However, the holding station maybe of any type (for example, a recess, a socket and so on) for holdingthe testing device in any removable way (for example, freely, snapfitted, with a selective blocking system and so on).

In an embodiment, the luminescence imaging apparatus comprises a furtherholding station for holding the imaging head in an acquisition positionin a removable manner. However, the further holding station may be ofany type (for example, a ring, a hook and so on, either separate orcombined with the holding station) for holding the imaging head in anyremovable way (for example, freely, snap fitted, with a selectiveblocking system and so on).

In an embodiment, the testing device in the imaging position fallswithin the field of view of the imaging head in the acquisitionposition. However, the testing device may fall within the field of viewin any way (for example, in a fixed or variable way in one or moredimensions, and so on).

In an embodiment, a center of the testing device in the imaging positionis on an optical axis of the imaging head in the acquisition position.However, the possibility of having the testing device in one or moredifferent positions is not excluded.

An embodiment provides a luminescence imaging system comprising theabove-mentioned luminescence imaging apparatus and testing device (fortesting the luminescence imaging apparatus). However, the testing devicemay be put on the market as a stand-alone product for use with anypre-existing luminescence imaging apparatus.

Generally, similar considerations apply if the testing device, theluminescence imaging apparatus and the luminescence imaging system eachhas a different structure or comprises equivalent components or it hasother operative characteristics. In any case, every component thereofmay be separated into more elements, or two or more components may becombined together into a single element; moreover, each component may bereplicated to support the execution of the corresponding operations inparallel. Moreover, unless specified otherwise, any interaction betweendifferent components generally does not need to be continuous, and itmay be either direct or indirect through one or more intermediaries.

1. A method for testing a luminescence imaging apparatus with a testingdevice placed within a field of view of an imaging head of theluminescence imaging apparatus, the testing device an imaging surfacefor imaging the testing device with one or more sites each comprising atleast one luminescence substance, wherein the method comprises, underthe control of a control unit of the luminescence imaging apparatus:acquiring, with a photograph camera of the imaging head, a photographimage of the field of view representative of a reflected light beingreflected by the field of view, retrieving a descriptor of the testingdevice comprising an indication of a geometry of the testing device andof a position of the sites in the testing device, finding a position ofthe testing device in the photograph image according to the geometry ofthe testing device, calculating a position of the sites in thephotograph image according to the position of the testing device in thephotograph image and the position of the sites in the testing device,acquiring, with a luminescence camera of the imaging head, aluminescence image of the field of view representative of a luminescencelight being emitted by the luminescence substance of the sites inresponse to an excitation light thereof provided by an excitation lightsource of the imaging head, determining a representation of the sites inthe luminescence image according to the position of the sites in thephotograph image, and testing the luminescence imaging apparatusaccording to the representation of the sites in the luminescence image.2. The method according to claim 1, wherein the testing device (110) hasone or more optically machine-readable positional markers at the imagingsurface, the method comprising, under the control of the control unit:retrieving the descriptor comprising a specification of the positionalmarkers and of a position of the sites with respect to the positionalmarkers, finding a position of the positional markers in the photographimage according to the specification of the positional markers, andcalculating the position of the sites in the photograph image accordingto the position of the positional markers in the photograph image andthe position of the sites with respect to the positional markers
 3. Themethod according to claim 1, wherein the method comprises, under thecontrol of the control unit: testing the luminescence imaging apparatusaccording to a comparison of the representation of each of the sites inthe luminescence image with at least one nominal value.
 4. The methodaccording claim 1, wherein the method comprises, under the control ofthe control unit: testing the luminescence imaging apparatus accordingto a comparison of the representation of each of the sites in theluminescence image with the representation of at least another one ofthe sites in the luminescence image.
 5. The method according to claim 1,wherein the method comprises, under the control of the control unit:determining a representation of a background area, different from therepresentations of the sites, in the luminescence image, and testing theluminescence imaging apparatus according to a comparison of therepresentation of each of the sites in the luminescence image with therepresentation of the background area in the luminescence image.
 6. Themethod according to claim 1, wherein the testing device comprises one ormore containers corresponding to the sites each filled with a liquidcomprising the corresponding luminescence substance, the methodcomprising, under the control of the control unit: estimating expectedtypes of the corresponding containers according to a comparison of therepresentations of the sites in the luminescence image with a pluralityof pre-defined specifications of possible types of the containers. 7.The method according to claim 1, wherein the testing device has one ormore optically machine-readable informative markers at the imagingsurface, the method comprising, under the control of the control unit:determining a representation of the informative markers in thephotograph image, determining device information relating to the testingdevice according to the representation of the informative markers, andtesting the luminescence imaging apparatus according to the deviceinformation.
 8. The method according to claim 7, wherein the testingdevice comprises one or more containers corresponding to the sites eachfilled with a liquid comprising the corresponding luminescencesubstance, the method comprising, under the control of the control unit:determining expected types of the containers according to the deviceinformation.
 9. The method according to claim 6, wherein the methodcomprises, under the control of the control unit (205): testing(754-772) the luminescence imaging apparatus (105) according topre-defined specifications of the expected types of the containers(325).
 10. The method according to claim 6, wherein the methodcomprises, under the control of the control unit: determining arepresentation of corresponding end portions, of the containersprojecting from corresponding seats of the testing device, in thephotograph image, and verifying a configuration of the testing deviceaccording to a matching of the representation of the end portions in thephotograph image with pre-defined definitions of the correspondingexpected types of the containers.
 11. The method according to claim 1,wherein the method comprises, under the control of the control unit:finding a position of the testing device in the luminescence image, andtesting the luminescence imaging apparatus according to an alignmentbetween the photograph image and the luminescence image determinedaccording to the position of the testing device in the photograph imageand the position of the testing device in the luminescence image. 12.The method according to claim 7, wherein the method comprises, under thecontrol of the control unit: retrieving one or more usage rules of thetesting device, and enabling said testing the luminescence imagingapparatus according to the usage rules.
 13. The method according toclaim 1, wherein the method comprises, under the control of the controlunit: retrieving usage information of one or more previous executions ofsaid testing the luminescence imaging apparatus, enabling said testingthe luminescence imaging apparatus according to the usage information,and saving the usage information of said testing the luminescenceimaging apparatus.
 14. The method according to claim 12, wherein themethod comprises, under the control of the control unit: retrieving theusage rules and/or the usage information according to the deviceinformation.
 15. The method according to claim 1, wherein the testingdevice comprises a testing light source at the imaging surface forgenerating a testing light corresponding to the luminescence light, themethod comprising, under the control of the control unit: acquiring afurther luminescence image of the field of view with the luminescencecamera while the excitation light source turned off and the testinglight source is turned on, and testing an acquisition unit of theimaging head for acquiring the luminescence images according to thefurther luminescence image and predefined characteristics of the testinglight source.
 16. The method according to claim 15, wherein the methodcomprises: testing an illumination unit of the imaging head forgenerating the excitation light according to a result of said testingthe luminescence imaging apparatus and a result of said testing theacquisition unit.
 17. The method according to claim 1, wherein themethod comprises, under the control of the control unit: determining adisplacement of the testing device and/or the imaging head from a targetposition according to the position of the testing device in thephotograph image, and outputting an indication of a movement of thetesting device and/or the imaging head for reaching the target positionaccording to the displacement thereof on an output unit of theluminescence imaging apparatus.
 18. The method according claim 1,wherein the method comprises, under the control of the control unit:outputting an indication of a result of said testing the luminescenceimaging apparatus on an output unit of the luminescence imagingapparatus.
 19. The method according to claim 1, wherein the methodcomprises, under the control of the control unit: transmitting anindication of a result of said testing the luminescence imagingapparatus to a remote computing system over a telecommunication network.20. The method according to claim 1, wherein the method comprises, underthe control of the control unit: repeating in a non-operative conditionof the luminescence imaging apparatus: acquiring a further photographimage of the field of view with the photograph camera, and searching arepresentation of the testing device in the further photograph imageaccording to the geometry of the testing device, until therepresentation of the testing device in the further photograph image hasbeen found, and triggering said testing the luminescence imagingapparatus in response to the representation of the testing device in thefurther photograph image being found.
 21. A computer readable mediumstoring instructions that when executed by a control unit of aluminescence imaging apparatus, cause the control unit; to acquire, witha photograph camera of an imaging head, a photograph image of a field ofview representative of a reflected light being reflected by the field ofview, to retrieve a description of the testing device comprising anindication of a geometry of the testing device and of a position of thesites in the testing device, to find a position of the testing device inthe photograph image according to the geometry of the testing device, tocalculate a position of the sites in the photograph image according tothe position of the testing device in the photograph image and theposition of the sites in the testing device, to acquire, with aluminescence camera of the imaging head, a luminescence image of thefield of view representative of a luminescence light being emitted bythe luminescence substance of the sites in response to an excitationlight thereof provided by an excitation light source of the imaginghead, to determine a representation of the sites in the luminescenceimage according to the position of the sites in the photograph image,and to test the luminescence imaging apparatus according to therepresentation of the sites in the luminescence image.
 22. A computerprogram product comprising a computer readable storage medium embodyinga computer program being loadable into a working memory of a controlunit of a luminescence imaging apparatus thereby configuring the controlunit, to acquire, with a photograph camera of am imaging head, aphotograph image of a field of view representative of a reflected lightbeing reflected by the field of view, to retrieve a description of thetesting device comprising an indication of a geometry of the testingdevice and of a position of the sites in the testing device, to find aposition of the testing device in the photograph image according to thegeometry of the testing device, to calculate a position of the sites inthe photograph image according to the position of the testing device inthe photograph image and the position of the sites in the testingdevice, to acquire, with a luminescence camera of the imaging head, aluminescence light being emitted by the luminescence substance of thesites in response to an excitation light thereof provided by anexcitation light source of the imaging head, to determine arepresentation of the sites in the luminescence image according to theposition of the sites in the photograph image, and to test theluminescence imaging apparatus according to the representation of thesites in the luminescence image.
 23. A luminescence imaging apparatus acontrol unit configured: to acquire, with a photograph camera of animaging head, a photograph image of a field of a view representation ofa reflected light being reflected by the field of view, to retrieve adescription of the testing device comprising an indication of a geometryof the testing device and of a position of the sites in the device, tofind a position of the testing device in the photograph image accordingto the geometry of the testing device, to calculate a position of thesites it the photograph image according to the position of the testingdevice in the photograph image and the position of the sites in thetesting device, to acquire, with a luminescence camera of the imaginghead, a luminescence image of the field of view representative of aluminescence light being emitted by the luminescence substance of thesites in response to an excitation light thereof provided by anexcitation light source of the imaging head, to determine arepresentation of the sites in the luminescence image according to theposition of the sites in the photograph image, and to test theluminescence imaging apparatus according to the representation of thesites in the luminescence image.
 24. The luminescence imaging apparatusaccording to claim 23, wherein the luminescence imaging apparatuscomprises: an imaging head, a supporting surface for resting the testingdevice, a holding station for holding the testing device an imagingposition on the supporting surface in a removable way, and a furtherholding station for holding the imaging head in an acquisition positionin a removable manner, the testing device in the imaging positionfalling within the field of view of the imaging head in the acquisitionposition.
 25. The luminescence imaging apparatus according to claim 23,wherein a center of the testing device in the imaging position is on anoptical axis of the imaging head the acquisition position.
 26. A testingdevice testing a luminescence imaging apparatus, wherein the testingdevice comprises: an imaging surface for imaging the testing device, theimaging surface being provided with one or more sites each comprising atleast one luminescence substance, and one or more opticallymachine-readable positional markers at the imaging surface fordetermining a position of the testing device.
 27. A luminescence imagingsystem comprising a luminescence imaging apparatus and a testing devicefor testing the luminescence imaging apparatus, the testing devicecomprising: an imaging surface for imaging the testing device theimaging surface being provided with one or more sites each comprising atleast one luminescence substance, and one or more opticallymachine-readable positional markers at the imaging surface fordetermining a position of the testing device.